Useful Links for the Medical Community
Medical and Research Papers
This section covers interesting research on Rh disease as well as an overview of the current world situation.
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Abstracts in PDF.
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Citation:
Ling, L.E., Hillson, J.L., Tiessen, R.G., Bosje, T., van Iersel, M.P., Nix, D.J., Markowitz, L., Cilfone, N.A., Duffner, J., Streisand, J.B., Manning, A.M. and Arroyo, S. (2019), M281, an Anti‐FcRn Antibody: Pharmacodynamics, Pharmacokinetics, and Safety Across the Full Range of IgG Reduction in a First‐in‐Human Study. Clin. Pharmacol. Ther., 105: 1031-1039. doi: 10.1002/cpt.1276. Epub 2018 Dec 4. PMID: 30402880; PMCID: PMC6587432.
Summary:
Previous work showed that endothelial cell expression of FcRn, the neonatal Fc receptor, prevents the intracellular degradation of IgG, thereby extending its circulatory half-life. This led to the development of M281, an anti-FcRn monoclonal antibody, which, in ex-vivo experiments, produced a transient and global increase in IgG clearance and reduced trans-placental IgG transmission. The current paper describes the first-in-human Phase I trial of M281 in 50 healthy subjects, in which they found an ~85% reduction in circulating IgG in the multiple dose arm, no effects on non-IgG antibody levels, and a similar incidence of adverse events in both the placebo and treatment groups. Although these initial results are very promising, due to the limited size of the study in otherwise healthy research subjects, further safety profiling, especially in pregnant mothers, fetuses, and immunocompromised patients, remains necessary.
Weblink:
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Citation:
Baker JM, Campbell DM, Pavenski K, Gnanalingam A, Hollamby K, Jegathesan T, Zipursky A, Bhutani V, Sgro M; NeoHBC. Infants affected by Rh sensitization: A 2-year Canadian National Surveillance Study. Paediatr Child Health. 2020 Mar 30;26(3):159-165. doi: 10.1093/pch/pxaa025. PMID: 33936335; PMCID: PMC8077204.
Summary:
Although the number of cases of Rh disease in the US, Canada, and Western Europe remain relatively low, it remains important to characterize the disease in these settings. Utilizing an extensive survey of pediatricians throughout Canada, this paper identified 62 cases of Rh disease between 2016 and 2018. Demographics, lab values, and treatment outcomes were assessed in detail, identifying an occurrence of Rh disease of ~8 out of every 100,000 births in Canada. Of note, almost 25% of Canadian cases occurred in immigrant mothers, highlighting the need for increased global prophylactic and education measures. Additionally, they noted that this number is likely an underestimate, given the 85% response rate, exclusive survey of pediatricians only, lack of miscarriage data, and the possibility of unrecognized cases.
Weblink:
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Citation:
Escamilla-Rivera V, Santhanakrishnan M, Liu J, Gibb DR, Forsmo JE, Foxman EF, Eisenbarth SC, Luckey CJ, Zimring JC, Hudson KE, Stowell SR, Hendrickson JE. Complement Plays a Critical Role in Inflammation-Induced Immunoprophylaxis Failure in Mice. Front Immunol. 2021 Jun 25;12:704072. doi: 10.3389/fimmu.2021.704072. PMID: 34249009; PMCID: PMC8270673.
Summary:
Polyclonal anti-KEL immunoglobulin has been demonstrated to prevent alloimmunization. However, breakthrough cases can occur when the recipient is in a state of viral-like inflammation. Escamilla-Rivera et al (2021) examine the mechanism for this failure. In a murine model, they demonstrate a “two-hit” model in which complement (C3 and C1q) and complement receptors (CR1 and CR2) are required for alloantibody production in the setting of anti-KEL immunoglobulin and a virus-like stimulus. This may have translational relevance to immunoprophylaxis failure with anti-Rh(D) immunoglobulin.
Link (free access):
https://www.frontiersin.org/articles/10.3389/fimmu.2021.704072/full
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Citation:
Alshehri AA, Jackson DE. Non-Invasive Prenatal Fetal Blood Group Genotype and Its Application in the Management of Hemolytic Disease of Fetus and Newborn: Systematic Review and Meta-Analysis. Transfus Med Rev. 2021 Apr;35(2):85-94. doi: 10.1016/j.tmrv.2021.02.001. Epub 2021 Mar 1. PMID: 33781630.
Summary:
Non-Invasive Prenatal Testing (NIPT) has the potential to identify pregnancies at risk of developing Hemolytic Disease of the Fetus and Newborn (HFDN) by genotyping fetal RHD exons. In the absence of fetal RHD antigens, NIPT can reduce unnecessary anti-Rh(D) prophylaxis. Alshehri and Jackson (2021) find that RHD genotyping with NIPT can be highly sensitive and specific (99% and 98% at the 95% confidence level, respectively) under appropriate conditions.
NCBI Link (not free access):
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Citation:
Yu M, Tang T, Zheng R, Situ M, Feng J. A comparative study on perinatal outcomes of red blood cell-alloimmunized pregnancies with anti-RhD in combination and anti-RhD alone in China. Vox Sang. 2022 Feb;117(2):268-274. doi: 10.1111/vox.13161. Epub 2021 Jun 10. PMID: 34111300.
Summary:
In a retrospective, single-center study of 165 alloimmunized women in Guangzhou, China, Yu et al. (2020) examined whether perinatal outcomes differed between pregnancies alloimmunized with anti-RhD (n=133) alone versus anti-RhD in combination with anti-RhC or anti-RhE (n=32). Fetuses of combination pregnancies were significantly more likely to be anemic and require intrauterine transfusions than fetuses of anti-RhD only pregnancies. Fetuses of combination pregnancies were also more likely to require simple transfusions, but there was no difference observed for exchange transfusions. This study suggests that fetuses of mothers with both anti-Rh antibodies and antibodies against other Rh-family antigens may be at increased risk of requiring intrauterine and simple transfusions.
NCBI Link (not free access):
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Hemolytic disease of the fetus and newborn due to Rh(D) incompatibility: A preventable disease that still produces significant morbidity and mortality in children
Valeria Pegoraro, Ducciocompet Urbinati, Gerard H. A. Visser, Gian Carlo Di Renzo, Alvin Zipursky, Brie A. Stotler, Steven L. Spitalnik
This interesting study brings to light the fact that even though anti-Rh(D) has been given regulatory approval in 1968, around 50% of women around the world still don’t have access to this immunoprophylaxis.
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Provider guidelines
We are compiling a list of useful guidelines for care providers.
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This comprehensive guideline gives information about Rh disease, its causes, symptoms, diagnosis and treatment/management.
Useful Links for Rh-negative Women and Families
If you are considering a pregnancy or are already pregnant, here is a list of useful and accessible information and links.
Promotional Material
You will find some useful WIRhE visuals should you wish to promote our initiatives in your region of the world.
Video
Here are some engaging videos to discover more about the Rh disease, Rh disease eradication projects around the world and the WIRhE initiative.
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Steven Spitalnik, MD and Executive Director of WIRhE gives a talk about the Rh disease’s heavy toll in the world today and the reasons why the WIRhE consortium was created. This talk was given at the South Central Association of Blood Banks on August 28, 2020.
View on Youtube